The present invention is directed to a method for rapid screening of reactants, catalysts, and associated process conditions and, more specifically, to a method of producing a chemical reaction that emulates those carried out in production-scale, continuous flow or continuous stirred tank reactors.
Since its introduction in 1970, combinatorial chemistry has become a popular research tool among scientists in many fields. High throughput and combinatorial screening for biological activity have been prevalent in the pharmaceutical industry for nearly twenty years, and more recently, high throughput and combinatorial screening for improved catalysts for the bulk chemical industries have enjoyed increasing popularity.
A substantial reason for the lag in the development of high throughput and combinatorial screening for production scale reactions is the difficulty in emulating the production-scale reactions at the micro-scale necessary for high throughput or combinatorial work. In particular, special problems can arise for reactions that are significantly dependent on flow rate or configuration.
Most combinatorial work to date has focused on xe2x80x9csolid phasexe2x80x9d reactions. It is known that a wide variety of organic reactions can be carried out on substrates immobilized on resins. However, a substantial number of production scale reactions are xe2x80x9cliquid phasexe2x80x9d or xe2x80x9cmixed phasexe2x80x9d and, as noted, are carried out in continuous flow reactor systems.
Early efforts in high throughput screening of solutions have focused on catalyst screening. Before the application of the high throughput and combinatorial approaches, catalyst testing was traditionally accomplished in bench scale or larger pilot plants in which the feed to a continuous flow reactor was contacted with a catalyst under near steady state reaction conditions. However, rapid and combinatorial screening of reactants, catalysts, and associated process conditions require that a large number of reactions or catalytic systems be tested simultaneously. In certain applications, screening-level data can be generated by using miniaturized batch reactors in conjunction with liquid-handling robots that aliquot the appropriate catalysts and reactants to each vial or reaction well. In other applications, however, batch reactions do not behave in the same fashion as continuous flow reactions and could provide misleading results if the goal of screening is to identify reactants or catalyst systems that will be implemented in production-scale continuous flow reactors.
As the demand for bulk chemicals has continued to grow, new and improved methods of producing more product with existing resources are needed to supply the market. Unfortunately, the identities of additional effective reactants and catalyst systems for these processes continue to elude the industry. What are needed are new and improved methods and devices for rapid screening of potential reactants, catalysts, and associated process conditions.
Accordingly, the present invention is directed to a method for producing a chemical reaction in a manner useful for rapid screening of reactants, catalysts, and associated process conditions.
In a particular embodiment, the present invention is directed to a method for producing a chemical reaction between a monohydroxyaromatic compound and an aldehyde or ketone to produce a bisphenol in a batch reactor emulating the conditions of a continuous flow reactor by incremental flow, the method comprising the steps of:
a) providing a reaction vessel and reactants;
b) placing reactants in the reaction vessel;
c) allowing the reaction to proceed for a time interval;
d) withdrawing a volume increment of the reaction mixture comprising at least one of the reactants from the reaction vessel;
e) adding a volume increment of at least one of the reactants to the reaction vessel; and
f) repeating steps c), d), and e) until the reaction reaches a substantially steady state, as shown by analysis.
In alternative embodiments, the volume increment withdrawal can take place before, after, or contemporaneously with the volume increment addition.